Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens.

Abstract

In the current study, we investigated whether Staphylococcus aureus grown from affected skin of atopic dermatitis (AD) patients secreted identifiable toxins that could act as allergens to induce IgE-mediated basophil histamine release. The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1). S. aureus isolates from 24 of 42 AD patients secreted identifiable toxins with SEA, SEB, and TSST accounting for 92% of the isolates. 32 of 56 AD sera (57%) tested contained significant levels of IgE primarily to SEA, SEB, and/ or TSST. In contrast, although SEA, SEB, or TSST secreting S. aureus could be recovered from the skin of psoriasis patients, their sera did not contain IgE antitoxins.Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE. Basophils from eight other AD patients and six normal controls who had no IgE antitoxin failed to demonstrate toxin-induced basophil histamine release. Stripped basophils sensitized with three AD sera containing IgE to toxin released 1541% of total basophil histamine only when exposed to the relevant toxin, but not to other toxins. Sensitization of basophils with AD sera lacking IgE antitoxin did not result in release of histamine to any of the toxins tested.These data indicate that a subset of patients with AD mount an IgE response to SEs that can be grown from their skin. These toxins may exacerbate AD by activating mast cells, basophils, and/or other Fce-receptor bearing cells armed with the relevant IgE antitoxin. (J. Clin. Invest. 1993Invest. . 92:1374Invest. -1380

Atopic Dermatitis

“…IgE antibodies directed against staphylococcal superantigens correlate with their skin disease severity 53 . Additionally it has been shown that binding of S. aureus to the skin is significantly enhanced by AD skin inflammation; scratching may enhance S. aureus binding by disturbing the skin barrier and isolated S. aureus was detected to possess an increased activity of ceramidase, thereby aggravating the skin barrier dysfunction.…”

Basis for the barrier abnormality in atopic dermatitis: Outside-inside-outside pathogenic mechanisms

“…Over time, nontoxigenic strains of S aureus that colonize patients with AD can be replaced by enterotoxin-generating strains, 82 which in turn could aggravate AD through at least 3 mechanisms (Fig 4): (1) toxigenic strains are more likely to produce clinical infections than are nontoxigenic strains 82 ; (2) some toxins stimulate pruritus 83 and production of specific IgE 15,[84][85][86]and (3) some toxins serve as "superantigens" that stimulate T-and B-cell proliferation, as well as immunoglobulin class-switching to allergen specific or "superallergens" that stimulate IgE production. 15,87 Activated T cells produce IL-31, which also induces pruritus.…”

New insights in the pathogenesis of atopic dermatitis

“…aureus, Malassezia species, and Candida albicans are important triggers of cutaneous inflammation of AD (3,53,54). These microbial pathogens may induce host production of superantigen-or pathogen-specific IgE, which leads to basophil activation and histamine release (55). S. aureus cell wall products also bind to TLR, leading to the production of TSLP by keratinocytes (56).…”